De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity.
De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity.
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DOI：
10.1126/science.aad8865
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发表时间：
2016-05-06
期刊：
影响因子：
--
通讯作者：
Baker D
中科院分区：
文献类型：
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作者：
Boyken SE;Chen Z;Groves B;Langan RA;Oberdorfer G;Ford A;Gilmore JM;Xu C;DiMaio F;Pereira JH;Sankaran B;Seelig G;Zwart PH;Baker D
在自然界中，DNA和蛋白质的结构特异性是完全不同的：在DNA中，特异性来自双螺旋核心的模块氢键，而在蛋白质中，特异性主要来自隐藏的疏水包装，辅之以不规则的外围极性相互作用。在这里，我们描述了一个通用的方法来设计一个广泛的蛋白质同源寡聚体的特异性由模块化阵列的中心氢键网络。我们使用的方法来设计二聚体，三聚体，和四聚体组成的两个同心环的螺旋，包括以前没有见过的三角形，正方形，和超螺旋拓扑结构。X射线晶体学证实，结构的整体，特别是氢键网络，是几乎相同的设计模型，和网络赋予在体内的相互作用特异性。设计具有原子精度的广泛氢键网络的能力是蛋白质设计的一个里程碑，并且能够为广泛的合成生物学应用编程蛋白质相互作用特异性。
In nature, structural specificity in DNA and proteins is encoded quite differently: in DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen bond networks. We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall, and the hydrogen bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen bond networks with atomic accuracy is a milestone for protein design and enables the programming of protein interaction specificity for a broad range of synthetic biology applications.